Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least one F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor.

OBJECTIVE: To describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers. STUDY DESIGN: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period. RESULTS: Among 608 patients on ETI, 109 (17.9%) reported at least one AE. The majority (N=85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs. 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA p-value 0·026). CONCLUSIONS: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted.

The Alcohol Harm Paradox in Periodontitis.

Individuals of lower socioeconomic position (SEP) experience a greater rate of alcohol-related harms, yet they consume equal or lower amounts of alcohol than higher-SEP individuals. This phenomenon, called the "alcohol harm paradox" (AHP), gained attention recently, and different mechanisms have been proposed to explain it. Since both SEP and alcohol have been suggested to be associated with periodontitis risk, we conducted a secondary analysis using data from the National Health and Nutrition Examination Survey 2011 to 2012 and 2013 to 2014 cycles, aiming to examine 1) whether the association between alcohol consumption and periodontitis is modified by SEP and 2) the extent to which the effect of SEP inequalities on periodontitis is mediated by and/or interacts with alcohol consumption. We set educational attainment as the main SEP proxy and tested the poverty income ratio in subsequent sensitivity analyses. Effect measure modification analysis was employed, considering heavy drinking as exposure, and causal mediation analysis based on the potential outcome's framework decomposed the effect of SEP on periodontitis in proportions attributable to mediation and interaction. Models were fitted using binary logistic regression and adjusted for sex, ethnicity, age, body mass index, smoking status, diabetes, binge drinking, and regular preventive dental visits. The analytical sample comprised 4,057 participants. After adjusting for covariates, less educated heavy drinkers presented 175% (odds ratio, 2.75; 95% confidence interval [CI], 2.04-3.72) higher odds of periodontitis than their counterparts, and super-additive associations were found (relative excess risk due to interaction: 1.35; 95% CI, 0.49-2.20). Additionally, -69.5% (95% CI, -122.1% to -16.8%) of the effects of education on periodontitis were attributable to interaction with heavy drinking, consistent with the AHP. No contribution was found for the mechanism of mediation. Heavy drinking disproportionately impacts the occurrence of periodontitis in lower-SEP individuals. Lower-SEP individuals seem to experience differential effects of heavy drinking on periodontitis.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Electroanatomical voltage mapping with contact force sensing for diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Three-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Yet, previous studies utilizing EAM have not systematically used contact-force sensing catheters (CFSC) to characterize the substrate in ARVC, which is the current gold standard to assure adequate tissue contact. OBJECTIVE: To investigate reference values for endocardial right ventricular (RV) EAM as well as substrate characterization in patients with ARVC by using CFSC. METHODS: Endocardial RV EAM during sinus rhythm was performed with CFSC in 12 patients with definite ARVC and 5 matched controls without structural heart disease. A subanalysis for the RV outflow tract (RVOT), septum, free-wall, subtricuspid region, and apex was performed. Endocardial bipolar and unipolar voltage amplitudes (BVA, UVA), signal characteristics and duration as well as the impact of catheter orientation on endocardial signals were also investigated. RESULTS: ARVC patients showed lower BVA vs. controls (p = 0.018), particularly in the subtricuspid region (1.4, IQR:0.5-3.1 vs. 3.8, IQR:2.5-5 mV, p = 0.037) and RV apex (2.5, IQR:1.5-4 vs. 4.3,IQR:2.9-6.1 mV, p = 0.019). BVA in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC 59-78%, p < 0.05 for all), with the highest performance for the subtricuspid region (AUC 78%, 95% CI:0.75-0.81, p < 0.001, negative predictive value 100%). A positive correlation between BVA and an orthogonal catheter orientation (46°-90°:r = 0.106, p < 0.001), and a negative correlation between BVA and EGM duration (r = -0.370, p < 0.001) was found. CONCLUSIONS: EAM using CFSC validates previous bipolar cut-off values for normal endocardial RV voltage amplitudes. RV voltages are generally lower in ARVC as compared to controls, with the subtricuspid area being commonly affected and having the highest discriminatory power to differentiate between ARVC and healthy controls. Therefore, EAM using CFSC constitutes a promising tool for diagnosis of ARVC.

Microfluidic-based skin-on-chip systems for safety assessment of nanomaterials.

The skin is the body's largest organ, continuously exposed to and affected by natural and anthropogenic nanomaterials (materials with external and internal dimensions in the nanoscale range). This broad spectrum of insults gives rise to irreversible health effects (from skin corrosion to cancer). Organ-on-chip systems can recapitulate skin physiology with high fidelity and potentially revolutionize the safety assessment of nanomaterials. Here, we review current advances in skin-on-chip models and their potential to elucidate biological mechanisms. Further, strategies are discussed to recapitulate skin physiology on-chip, improving control over nanomaterials exposure and transport across cells. Finally, we highlight future opportunities and challenges from design and fabrication to acceptance by regulatory bodies and industry.

Co-occurrence of Periodontitis and Diabetes-Related Complications.

Periodontitis is a common finding among people with diabetes mellitus (DM) and has been cited as a DM complication. Whether and how periodontitis relates to other diabetes-related complications has yet to be explored. This study aims to examine the clustering of periodontitis with other diabetes-related complications and explore pathways linking diabetes-related complications with common risk factors. Using data from participants with DM across 3 cycles of the National Health and Nutrition Examination Survey (NHANES) (n = 2,429), we modeled direct and indirect pathways from risk factors to diabetes-related complications, a latent construct comprising periodontitis, cardiovascular diseases, proteinuria, and hypertension. Covariates included age, sex, socioeconomic status (SES), smoking, physical activity, healthy diet, alcohol consumption, hemoglobin A1c (HbA1c), dyslipidemia, and body mass index (BMI). Sensitivity analyses were performed considering participants with overweight/obesity and restricting the sample to individuals without DM. Periodontitis clustered with other diabetes complications, forming a latent construct dubbed diabetes-related complications. In NHANES III, higher HbA1c levels and BMI, older age, healthy diet, and regular physical activity were directly associated with the latent variable diabetes-related complications. In addition, a healthy diet and BMI had a total effect on diabetes-related complications. Although sex, smoking, dyslipidemia, and SES demonstrated no direct effect on diabetes-related complications in NHANES III, a direct effect was observed using NHANES 2011-2014 cycles. Sensitivity analysis considering participants with overweight/obesity and without DM showed consistent results. Periodontal tissue breakdown seems to co-occur with multiple diabetes-related complications and may therefore serve as a valuable screening tool for other well-known diabetes-related complications.

Radiotherapy skin marking with lancets versus electric marking pen - Comfort, satisfaction, effectiveness and cosmesis results from the randomized, double-blind COMFORTATTOO trial.

INTRODUCTION: Set-up skin markings are performed, in several centers, for radiotherapy (RT) treatments. This study aimed to compare two permanent methods: lancets and an electric marking pen, the Comfort Marker 2.0® (CM). METHODS: This was a prospective, unicentric, randomized study. Patients aged 18 years or older referred to our department to receive RT were recruited. Patients were randomly assigned, in a 1:1 ratio, to receive set-up markings using lancets or CM. The markings arrangement followed our departmental protocols. The coprimary endpoints were patients' comfort and effectiveness. Secondary endpoints included radiation therapists (RTTs) satisfaction and cosmesis. RESULTS: Between October 2021 and January 2022, 100 patients were enrolled (50 received lancets and 50 CM) and assessed for the comfort and satisfaction outcomes. CM was significantly less painful than the lancets, with 44% and 16% of the patients, respectively, considering the tattooing process painless (RR = 2.75; 95% IC: 1.36 - 5.58). On the RTT-reported satisfaction, CM had significantly easier processes than lancets (98.0% vs. 78.0%, respectively; RR = 1.26; 95% CI: 1.08 - 1.46). For effectiveness and cosmesis assessment, 98 patients were analyzed (48 received lancets and 50 CM). Patients receiving CM had a significantly higher proportion of markings graded as good and excellent compared to those receiving lancets (98.0% and 50.0%, respectively, had ≥75% of the tattoos assessed as good/excellent, RR = 1.96; 95% CI: 1.47 - 2.61). On the cosmetic evaluation, patients receiving CM had significantly better cosmetic markings, with a median score of 4.4 (vs. 3.5 for lancets, p <0.001). CONCLUSION: The trial results demonstrated that tattooing with the CM is significantly less painful, more effective, easier to apply, and cosmetically superior to tattooing with lancets. IMPLICATIONS FOR PRACTICE: Tattooing with CM allows for better results regarding pain, quality, ease and cosmesis.

Breast cancer patient-reported outcomes on level 1 and level 2 oncoplastic procedures using BREAST-Q®.

PURPOSE: In breast cancer management not only mortality and surgical morbidity measurements are important but also patient satisfaction indexes. The authors evaluated the satisfaction and health-related quality of life (HRQOL) using the breast-conserving therapy (BCT) and breast reduction (BR) modules of BREAST-Q®. METHODS: This is a cross-sectional study that analyzed breast cancer patients consecutively submitted to breast surgery between January 2011 and April 2018 using two modules of BREAST-Q®. 968 patients were contacted and 232 answers were gathered: 171 patients submitted to oncoplastic level 1 surgery answered the BCT module and 61 submitted to oncoplastic level 2 surgery answered the BR module. Clinical data were retrieved from patients' medical records. RESULTS: Among the 232 questionnaires received, the median scores for psychosocial well-being, sexual well-being and (postoperative) satisfaction with breasts for BCT and BR modules were, respectively, 77.0 and 73.5 (p = 0.17); 62.0 and 53.0 (p = 0.14); 72.0 and 66.0 (p = 0.66). The median of adverse effects of radiation in the BCT module was 87.0. The median satisfaction with outcome in the BR module was 86.0. Both groups of patients revealed high scores of satisfaction with care. For the BCT patients, satisfaction with breasts strongly correlated with sexual well-being and was moderately correlated with psychosocial and physical well-being. For the BR patients, the satisfaction with outcome strongly correlated with satisfaction with medical team and moderately correlated with the remaining scales. CONCLUSION: Both oncoplastic surgery levels yielded similar satisfaction outcomes when assessed using BCT and BR modules of BREAST-Q®.

Evaluation of antioxidant, photoprotective and antinociceptive activities of Marcetia macrophylla extract: potential for formulation of sunscreens

Abstract The antioxidant, photoprotective and antinociceptive Marcetia macrophylla active extract was investigated as an active ingredient in a sunscreen cream formulation. Thus, the M. macrophylla extract showed IC50 of 3.43 mg/ml of the antioxidant (DPPH scavenging test) and Sun Protection Factor of 20.25 (SPF/UV-B, at 250 µg/ml) and UV-A of 78.09% (photobleaching trans-resveratrol test). The antinociceptive activity was superior to all standards tested using the in vivo acetic acid-induced writhing test (99.14% at the dose of 200 mg/kg) and the high-performance liquid chromatography coupled with diode array detector and mass spectroscopy multi-stage (HPLC-DAD-MS/MS) enabled the structural characterization of the quercetin-3-O-hexoside, quercetin-3-O-pentoside and quercetin-3-O-desoxihexoside. The pharmaceutical formulation containing the Marcetia macrophylla crude active extract was prepared and the physicochemical tests (organoleptic characteristics, pH analysis and centrifugation), the in vitro UVB (sun protection factor, SPF) and UVA (-carotene) using the spectroscopic method were investigated. The formulation showed satisfactory results concerning the physicochemical parameters evaluated and active against the UV test. Thus, M. macrophylla showed biological activities with potential use in pharmaceutical preparations.

Resumo O extrato bruto de Marcetia macrophylla mostrou atividade antioxidante, fotoprotetora e antinociceptiva, sendo em seguida investigado como ingrediente ativo em uma formulação fotoprotetora. Assim, o extrato de M. macrophylla apresentou atividade antioxidante com IC50 de 3,43 mg/mL (teste de sequestro do DPPH) e Fator de Proteção Solar de 20,25 (FPS/UV-B, 250 µg/mL) e UV-A de 78,09% (teste de fotobranqueamento do trans-resveratrol). A atividade antinociceptiva usando o teste in vivo de contorções abdominais induzidas por ácido acético foi superior a todos os padrões testados (99,14% na dose de 200 mg/Kg). A análise por cromatografia líquida de alta eficiência acoplada a detector de fotodiodos e espectroscopia de massas multi-estágio (CLAE-DAD-EM/EM) possibilitou a caracterização dos flavonoides quercetina-3-O-hexosídeo, quercetina-3-O-pentosídeo e quercetina-3-O-desoxihexosídeo. A formulação farmacêutica contendo o extrato ativo bruto de Marcetia macrophylla foi preparada e os testes físico-químicos (características organolépticas, análise de pH e centrifugação), o UVB in vitro (fator de proteção solar, FPS) e UVA (-caroteno) foram investigados. A formulação apresentou resultados satisfatórios frente aos parâmetros físico-químicos avaliados e ativos contra UV. Assim, M. macrophylla apresentou atividades biológicas com potencial uso em preparações fitofarmacêuticas.

Evaluation of antioxidant, photoprotective and antinociceptive activities of Marcetia macrophylla extract: potential for formulation of sunscreens / Avaliação da atividade antioxidante, photoprotetora e antinociceptiva de Marcetia macrophylla: potencial formulação fotoprotetora

Abstract The antioxidant, photoprotective and antinociceptive Marcetia macrophylla active extract was investigated as an active ingredient in a sunscreen cream formulation. Thus, the M. macrophylla extract showed IC50 of 3.43 mg/ml of the antioxidant (DPPH∙ scavenging test) and Sun Protection Factor of 20.25 (SPF/UV-B, at 250 µg/ml) and UV-A of 78.09% (photobleaching trans-resveratrol test). The antinociceptive activity was superior to all standards tested using the in vivo acetic acid-induced writhing test (99.14% at the dose of 200 mg/kg) and the high-performance liquid chromatography coupled with diode array detector and mass spectroscopy multi-stage (HPLC-DAD-MS/MS) enabled the structural characterization of the quercetin-3-O-hexoside, quercetin-3-O-pentoside and quercetin-3-O-desoxihexoside. The pharmaceutical formulation containing the Marcetia macrophylla crude active extract was prepared and the physicochemical tests (organoleptic characteristics, pH analysis and centrifugation), the in vitro UVB (sun protection factor, SPF) and UVA (β-carotene) using the spectroscopic method were investigated. The formulation showed satisfactory results concerning the physicochemical parameters evaluated and active against the UV test. Thus, M. macrophylla showed biological activities with potential use in pharmaceutical preparations.

Resumo O extrato bruto de Marcetia macrophylla mostrou atividade antioxidante, fotoprotetora e antinociceptiva, sendo em seguida investigado como ingrediente ativo em uma formulação fotoprotetora. Assim, o extrato de M. macrophylla apresentou atividade antioxidante com IC50 de 3,43 mg/mL (teste de sequestro do DPPH∙) e Fator de Proteção Solar de 20,25 (FPS/UV-B, 250 µg/mL) e UV-A de 78,09% (teste de fotobranqueamento do trans-resveratrol). A atividade antinociceptiva usando o teste in vivo de contorções abdominais induzidas por ácido acético foi superior a todos os padrões testados (99,14% na dose de 200 mg/Kg). A análise por cromatografia líquida de alta eficiência acoplada a detector de fotodiodos e espectroscopia de massas multi-estágio (CLAE-DAD-EM/EM) possibilitou a caracterização dos flavonoides quercetina-3-O-hexosídeo, quercetina-3-O-pentosídeo e quercetina-3-O-desoxihexosídeo. A formulação farmacêutica contendo o extrato ativo bruto de Marcetia macrophylla foi preparada e os testes físico-químicos (características organolépticas, análise de pH e centrifugação), o UVB in vitro (fator de proteção solar, FPS) e UVA (β-caroteno) foram investigados. A formulação apresentou resultados satisfatórios frente aos parâmetros físico-químicos avaliados e ativos contra UV. Assim, M. macrophylla apresentou atividades biológicas com potencial uso em preparações fitofarmacêuticas.

Evaluation of antioxidant, photoprotective and antinociceptive activities of Marcetia macrophylla extract: potential for formulation of sunscreens / Avaliação da atividade antioxidante, photoprotetora e antinociceptiva de Marcetia macrophylla: potencial formulação fotoprotetora

The antioxidant, photoprotective and antinociceptive Marcetia macrophylla active extract was investigated as an active ingredient in a sunscreen cream formulation. Thus, the M. macrophylla extract showed IC50 of 3.43 mg/ml of the antioxidant (DPPH∙ scavenging test) and Sun Protection Factor of 20.25 (SPF/UV-B, at 250 µg/ml) and UV-A of 78.09% (photobleaching trans-resveratrol test). The antinociceptive activity was superior to all standards tested using the in vivo acetic acid-induced writhing test (99.14% at the dose of 200 mg/kg) and the high-performance liquid chromatography coupled with diode array detector and mass spectroscopy multi-stage (HPLC-DAD-MS/MS) enabled the structural characterization of the quercetin-3-O-hexoside, quercetin-3-O-pentoside and quercetin-3-O-desoxihexoside. The pharmaceutical formulation containing the Marcetia macrophylla crude active extract was prepared and the physicochemical tests (organoleptic characteristics, pH analysis and centrifugation), the in vitro UVB (sun protection factor, SPF) and UVA (β-carotene) using the spectroscopic method were investigated. The formulation showed satisfactory results concerning the physicochemical parameters evaluated and active against the UV test. Thus, M. macrophylla showed biological activities with potential use in pharmaceutical preparations.

O extrato bruto de Marcetia macrophylla mostrou atividade antioxidante, fotoprotetora e antinociceptiva, sendo em seguida investigado como ingrediente ativo em uma formulação fotoprotetora. Assim, o extrato de M. macrophylla apresentou atividade antioxidante com IC50 de 3,43 mg/mL (teste de sequestro do DPPH∙) e Fator de Proteção Solar de 20,25 (FPS/UV-B, 250 µg/mL) e UV-A de 78,09% (teste de fotobranqueamento do trans-resveratrol). A atividade antinociceptiva usando o teste in vivo de contorções abdominais induzidas por ácido acético foi superior a todos os padrões testados (99,14% na dose de 200 mg/Kg). A análise por cromatografia líquida de alta eficiência acoplada a detector de fotodiodos e espectroscopia de massas multi-estágio (CLAE-DAD-EM/EM) possibilitou a caracterização dos flavonoides quercetina-3-O-hexosídeo, quercetina-3-O-pentosídeo e quercetina-3-O-desoxihexosídeo. A formulação farmacêutica contendo o extrato ativo bruto de Marcetia macrophylla foi preparada e os testes físico-químicos (características organolépticas, análise de pH e centrifugação), o UVB in vitro (fator de proteção solar, FPS) e UVA (β-caroteno) foram investigados. A formulação apresentou resultados satisfatórios frente aos parâmetros físico-químicos avaliados e ativos contra UV. Assim, M. macrophylla apresentou atividades biológicas com potencial uso em preparações fitofarmacêuticas.

Double blind randomized clinical trial comparing minimally- invasive envelope flap and conventional envelope flap on impacted lower third molar surgery.

BACKGROUND: The latest trend in surgery is to look for minimally invasive procedures, with fewer complications and a shorter recovery time. This study aims to compare the minimally- invasive envelope flap, with smaller incision and fewer dissection and the conventional envelope flap, with a 20mm incision, on impacted mandibular third molar surgery, focusing on the hypothesis that there were no differences in postoperative outcomes. MATERIAL AND METHODS: A double-blind randomized clinical trial was designed to compare both incisions, focused on determining the approach with minor postoperative side-effects and minor impact on quality-of-life. A total of 60 patients were enrolled for the study if their presented impacted mandibular third molar and was 18-years-old or more. Both groups were evaluated from time elapsed on the surgery, maximum mouth opening, swelling and quality of life assessment. RESULTS: The flap choice influenced facial swelling (p=0,03), pain on the first three days (p=0,037), interference with oral hygiene (p=0,019) and discomfort on speech (p=0,07). Chewing, swallowing, trismus, pain after seven days, postoperative complications and other quality-of-life arrangements were no different between groups. CONCLUSIONS: The minimally- invasive envelope flap could lead to a less painful experience for the patient, with fewer impact on the oral hygiene and speech discomfort.

Red and brown seaweeds extracts: A source of biologically active compounds.

The biological activities of Porphyra sp., Gracilaria gracilis, Alaria esculenta and Saccharina latissima extracts prepared by enzymatic and ball milling-assisted methods and hot water were evaluated. Enzyme-assisted methods allowed the highest extraction yields. Alcalase-assisted extraction (EAA) was the most effective in the recovery of polyphenolic compounds and Porphyra sp. had the highest content. The efficiency of flavonoids extraction was highly dependent on the used method. Globally, Porphyra sp. and EAA extracts exhibited the highest antioxidant and chelating activities. The highest α-amylase inhibitory activity was determined in HW Porphyra sp. extract while EAA A. esculenta extract had the highest α-glucosidase inhibitory activity. The highest ACE inhibitory activity was obtained in EAA from S. latissima. None of the extracts showed antimicrobial activity against the tested bacteria. The results showed that Porphyra sp. and S. latissima are potentially useful as ingredient in functional foods and nutraceuticals.

Initial experience with targeted axillary dissection after neoadjuvant therapy in breast cancer patients.

BACKGROUND: Targeted axillary dissection (TAD) combines sentinel node biopsy (SNB) with the removal of the previously marked metastatic node. TAD is a promising concept for axillary restaging in node-positive breast cancer patients with pathological complete response (pCR) to neoadjuvant therapy (NAT). We aimed to evaluate TAD feasibility in this context. METHODS: A prospective observational study was conducted in biopsy-confirmed cN1 patients. The removal of the clipped node (CN) was guided by intraoperative ultrasound. SNB used indocyanine green and patent blue V dye. If the CN or sentinel lymph nodes (SLN) had any metastatic foci, or the TAD procedure was unsuccessful, the patient underwent axillary lymph node dissection (ALND). RESULTS: Thirty-seven patients were included. TAD and SNB identification rates were 97.3%. Every retrieved CN was also a SLN. At the individual level, SNB identification rate was 89.2% with indocyanine green and 85.5% with patent blue V dye. The CN identification rate was 81.1%, being higher when the CN was localized on the intraoperative ultrasound (84.4% vs 60.0%). Nodal pCR was achieved by 54.1% of our patients and was more frequent in HER2-positive and triple-negative tumors (p = 0.039). Nineteen patients were spared from ALND. CONCLUSION: TAD with intraoperative ultrasound-guided excision of the CN and SNB with indocyanine green and patent blue V dye is a feasible concept to identify patients without axillary residual disease after NAT, that can be spared from ALND, although the need for marking the biopsied node should be further investigated.

Laparoscopic robotic-assisted restorative proctocolectomy and ileal J-pouch-anorectal anastomosis in children.

PURPOSE: Total proctocolectomy with ileal J-pouch-anorectal anastomosis (IPAA) remains the preferred surgical treatment for ulcerative colitis (UC) in children. Considering the well-known advantages of minimally invasive approach, and its main application for the deep pelvis, robotic surgery may be used in UC reconstructive procedures. The aim of the study is to report our experience with Robotic IPAA in children. METHODS: Single surgeon experience on Robotic IPAA were prospectively included. Data on patient demographics, surgical details, complications, and length of stay (LOS), were collected. RESULTS: Fifteen patients were included. Median age was 13.2 years, median body weight 45 kg. Median operative time was 240 min. Median LOS was 7 days and mean follow-up time 1 year. No intraoperative complication occurred. Five postoperative complications happened: 3 minors treated conservatively (CD I-II), 2 majors needing reintervention under anesthesia (CD IIIb). No mortality was observed. CONCLUSION: Our preliminary experience reveals that Robotic IPAA is a safe and feasible option for the surgical treatment of UC in children. A bigger patient sample and a long-term follow-up are needed to confirm our findings.

Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response.

The study is aimed at investigating if PUFA supplementation could prevent the effects of a short-term HFD on α7nAChR expression and on the severity of sepsis. Swiss mice were used for the in vivo experiments. For the in vitro experiments, we used a microglia cell line (BV-2) and a hepatoma cell line (Hepa-1c1c7) derived from mice. The animals were either fed standard chow, fed a short-term HFD (60%), or given supplementation with omega-3 fatty acid (2 g/kg or 4 g/kg bw) for 17 days, followed by a short-term HFD. Endotoxemia was induced with an intraperitoneal (i.p.) lipopolysaccharide injection (LPS, 5 or 12 mg/kg), and sepsis was induced by subjecting the animals to cecal ligation and puncture (CLP). BV-2 and Hepa-1c1c7 cells were treated with LPS (100 and 500 ng/mL, respectively) for 3 hours. RT-PCR or Western blotting was used to evaluate α7nAChR expression, inflammatory markers, DNMT1, and overall ubiquitination. LPS and HFD reduced the expression of α7nAChR and increased the expression of inflammatory markers. Omega-3 partially prevented the damage caused by the HFD to the expression of α7nAChR in the bone marrow and hypothalamus, decreased the inflammatory markers, and reduced susceptibility to sepsis-induced death. Exposing the BV-2 cells to LPS increased the protein content of DNMT1 and the overall ubiquitination and reduced the expression of α7nAChR. The inflammation induced by LPS in the BV-2 cell decreased α7nAChR expression and concomitantly increased DNMT1 expression and the ubiquitinated protein levels, indicating the participation of pre- and posttranscriptional mechanisms.

Effect of blood loss during caesarean section on coagulation parameters.

INTRODUCTION: Venous thrombosis is the leading cause of pregnancy-related maternal morbidity and mortality. The thrombosis risk is increased by caesarean section and blood loss, though underlying mechanisms of these prothrombotic changes remain unknown. MATERIALS AND METHODS: This prospective study recruited 50 pregnant women at term undergoing elective caesarean section at University Hospital Magdeburg, Germany. Blood loss during surgery was correlated with the changes in total protein S, full length TFPI (TFPIfl), prothrombin, the endogenous thrombin potential (ETP) and resistance to activated protein C (APCsr) determined via calibrated automated thrombography. RESULTS: Mean blood loss was 506 ml (95%CI: 456 to 557 ml). Total protein S was 0.63 (95%CI: 0.60 to 0.67) U/ml preoperatively, decreased by 14.8% after caesarean section and almost normalised five days later. TFPIfl was 0.47 (95%CI: 0.41 to 0.53) U/ml before, remained unchanged immediately after and increased by 11.5% five days after surgery. Prothormbin was 1.10 (95%CI: 1.03 to 1.16) U/ml preoperatively, reduced by 10.4% immediately after and increased again five days after caesarean section, exceeding the preoperative values by 4.4% (-0.7 to 9.6). The ETP decreased by 3.9%, whereas the APCsr increased by 37.0% immediately after caesarean section. The changes in total protein S, prothrombin, thrombin generation and APC resistance showed a trend to be more pronounced in the subgroups with higher blood loss. DISCUSSION: Moderate blood loss during caesarean section hardly reduces thrombin generation but aggravates pregnancy-induced APC resistance and combined deficiency of TFPI and protein S, which can account for the increased thrombosis risk in early puerperium.

Reproductive status effects of pair-housed male pigs on natural, agonistic and sexual behaviours.

Boar rearing, which avoids pain and suffering caused by surgical castration, provides better performance, a greater deposition of muscle tissue and leaner carcasses and thus has beneficial effects on both animal welfare and the product. Some countries that do not slaughter boars must consider their boar taint and aggressive and sexual behaviours. Considering that pigs are housed in large groups, which may complicate the formation of social hierarchies and increase fighting and mounting behaviours, some studies have conducted research with reduced numbers of pigs per pen, but these behaviours continued to be observed. However, a study of the reproductive status of pair-housed male pigs has yet to be reported. The aim of this study was to determine whether the reproductive status of uncastrated, immunocastrated and surgically castrated pair-housed male pigs alters their natural, agonistic and sexual behaviours. A total of 48 male pigs from Agroceres PIC™ genetics were assigned to three groups: surgically castrated (barrows), immunocastrated and uncastrated (boars). Natural, aggressive and sexual behaviours of the pigs were assessed by direct observations during four periods of 12 h each (six, five and three weeks before slaughter and the slaughter week). The pigs were housed in pairs from the growing phase until slaughter. Animal behaviour was observed from the finishing phase to slaughter. Carcass lesions were assessed according to five different classes (one: no injury; two to five: severely injured). Overall, boars spent more time lying and less time eating and drinking than barrows. In total of all the periods (48 h), boars expressed more aggressive and sexual behaviours than barrows, whereas immunocastrated pigs displayed similar behaviours to boars, before and after the second vaccine dose. No differences in carcass lesions between treatments and no prevalence of carcasses with severe injuries were observed. In conclusion, the reproductive status of pair-housed male pigs did not change the natural behaviour of boars, immunocastrated pigs or barrows. The agonistic and sexual behaviours of boars and barrows remained unchanged. When housing pigs in pairs, immunocastrated pigs presented similar agonistic and sexual behaviours to boars before and after the second immunocastration vaccine dose. The use of pair-housed uncastrated male pigs has generated welfare benefits for these animals, as the number of carcasses with injuries did not differ from barrows and immunocastrated pigs.

Cost-effectiveness of brentuximab vedotin in advanced stage Hodgkin's lymphoma: a probabilistic analysis.

BACKGROUND: Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) is a well-established therapy for advanced Hodgkin's lymphoma (HL). However, the recently completed ECHELON-1 trial showed potential net clinical benefit for brentuximab vedotin (BREN+AVD) compared to ABVD as frontline therapy in patients with advanced Hodgkin's lymphoma. The objective of this analysis is to determine whether, on current evidence, BREN+AVD is cost-effective relative to ABVD as frontline therapy in patients with advanced HL. METHODS: We constructed a probabilistic Markov model with two arms and six mutually exclusive health states, using six-month cycle lengths, and a 15-year time horizon. Time-dependent transition probabilities were calculated from 'real-world' data collected by the BC Cancer's Centre for Lymphoid Cancer database or from the literature for ABVD. Time-dependent transition probabilities for BREN+AVD were taken from the ECHELON-1 trial. We estimated the incremental cost and effects per patient of each therapy and calculated the incremental cost-effectiveness ratio (ICER). Costs were measured in 2018 Canadian dollars and effects measured in quality-adjusted life years (QALYs). A probabilistic analysis was used to generate a cost-effectiveness acceptability curve (CEAC). RESULTS: The incremental cost between standard therapy with ABVD and therapy with BREN+AVD was estimated to be $192,336. The regimen of BREN+AVD resulted in a small benefit in terms of QALYs (0.46 QALYs). The estimated ICER was $418,122 per QALY gained. The probabilistic analysis suggests very few (8%) simulations fall below $100,000 per QALY. Even at a threshold of $200,000 per QALY gained, there was only a 24% chance that BREN+AVD would be considered cost-effective. Sensitivity analyses evaluating price reductions for brentuximab showed that these reductions needed to be in excess of 70% for this regimen to be cost-effective at a threshold of $100,000 per QALY. CONCLUSIONS: There may be a clinical benefit associated with BREN+AVD, but on current evidence the benefit is not adequately substantive compared to ABVD therapy given the cost of brentuximab vedotin. Agencies responsible for making decisions about BREN+AVD as frontline therapy for patients with advanced HL should consider whether they are willing to implement this treatment given the current uncertainty and cost-benefit profile, or negotiate substantial price-reductions from the manufacturer should they choose to reimburse.